Two-Color Near-Infrared Fluorescence Guided Surgery Tools Enabling Simultaneous Cancer Margin and Nerve Visualization during Head and Neck Squamous Cell Carcinoma Resection

双色近红外荧光引导手术工具可在头颈鳞状细胞癌切除过程中同时实现癌症边缘和神经可视化

• 批准号: 10603689
• 负责人: Connor William Barth
• 金额: $ 38.62万
• 依托单位: TRACE BIOSCIENCES INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-23 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603689
• 关键词: Adipose tissue; Anatomy; Biological Sciences; Blood Vessels; Cancer Control; Clinical; Clinical Medicine; Clinical Trials; Collaborations; Color; Complex; Contrast Media; Detection; Development; Dose; Ensure; Epidermal Growth Factor Receptor; Excision; Face; Family suidae; Fascia; Fluorescence; Fluorescent Probes; Frequencies; Goals; Head Cancer; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Hour; Image; Image-Guided Surgery; Incidence; Injections; Integrins; Lead; Length; Letters; Life; Light; Malignant Neoplasms; Metalloproteases; Modeling; Muscle; Neck Cancer; Nerve; Normal tissue morphology; Operative Surgical Procedures; Outcome; Palpation; Patients; Peptides; Performance; Persistent pain; Pharmacology; Phase; Plague; Preclinical Testing; Procedures; Quality of life; Rattus; Recurrent Laryngeal Nerve; Reporter; Resolution; Rodent; Signal Transduction; Site; Spinal; Structure; Structure of phrenic nerve; Surgeon; Surgical margins; Survival Rate; System; Technology; Technology Assessment; Time; Tissues; Vagus nerve structure; Vertebral column; Visualization; Work; chromophore; clinical imaging; clinical translation; comorbidity; design; experience; falls; fluorescence imaging; fluorescence-guided surgery; fluorophore; head and neck cancer patient; imaging capabilities; imaging probe; imaging system; improved; innovation; intravenous administration; loss of function; manufacturing test; mouse model; nerve damage; neurotransmission; novel; preclinical development; preservation; small molecule; spared nerve; surgery outcome; targeted imaging; tool; tumor; uptake

PROJECT SUMMARY Head and neck squamous cell carcinoma (HNSCC) is the sixth highest incidence cancer worldwide, with >650,000 cases annually. Surgery is a primary treatment option for HNSCC, during which surgeons face two main goals: 1) complete cancer resection and 2) preservation of normal tissue structures such as muscle, blood vessels, and nerves to ensure post-surgical quality of life. Unfortunately, these goals are not synergistic, where complete cancer resection is often limited by efforts to preserve normal tissue and reduce life altering comorbidities. In fact, positive surgical margins are found in 20-30% of patients, and nerve damage represents a major surgical comorbidity, with 5-30% of patients experiencing lasting pain or loss of function. Currently, no technology exists to enhance intraoperative cancer and nerve recognition. Thus, technology to provide direct visualization of cancer margins and nerves simultaneously in real time would greatly improve surgical outcomes and reduce comorbidities for HNSCC patients. Fluorescence Guided Surgery (FGS) has successfully integrated into clinical medicine, providing surgeons real-time visualization of important tissues and complex anatomy. Using compact and high-resolution FGS imaging systems, which operate almost exclusively in the near-infrared (NIR, 700-900 nm), surgeons can image targeted fluorescent probes with high contrast at up to centimeter depths. NIR Nerve-specific and HNSCC-targeted probes under development would together provide an integrated FGS tool for HNSCC resection. Several peptide-based FGS imaging probes have demonstrated efficacy in identifying tumor margins and are currently in phase II and III clinical trials, including those targeting epidermal growth factor receptor (EGFR), matrix metalloprotease (MMP), and integrins. We have developed first-in-class NIR nerve-specific fluorescent small-molecule probes that demonstrate high nerve signal to all background tissues (e.g., muscle, adipose, vasculature, fascia, etc.) following intravenous administration in rodents and swine. Importantly, the tumor-targeting FGS probes utilize fluorescent reporters centered at 800-nm wavelengths, while our nerve-specific probes fluoresce at 700-nm wavelengths, providing spectrally distinct tissue detection and compatibility with existing two-color FGS systems. The combination of these two promising technologies would provide a comprehensive, innovative solution to enhance cancer control and nerve sparing during HNSCC resection. This study’s immediate milestones will include (1) characterization of our lead NIR nerve-specific fluorophore for head and neck procedures, (2) quantification of tumor- and nerve-specific FGS probe co-administration performance including cross-talk, and (3) assessment of this technology using a clinical two-color FGS system. This work will result in the first comprehensive FGS tool for cancer resection and nerve sparing during head and neck procedures. The proposed development will provide important proof-of-concept for further development and partnership. In Phase II, the first two-color tumor and nerve targeted FGS studies will be completed in patients undergoing HNSCC resection.

项目摘要 头颈部鳞状细胞癌（HNSCC）是全球第六大事件，有 >每年> 650,000例。手术是HNSCC的主要治疗选择，外科医生面对两个 主要目标：1）完整的癌症切除和2）保存正常组织结构，例如肌肉，血液 船只和神经，以确保手术后的生活质量。不幸的是，这些目标不是协同的 完全的癌症切除通常受到维护正常组织和降低寿命改变的努力的限制 合并症。实际上，在20-30％的患者中发现了阳性手术边缘，而神经损害代表 主要的手术合并症，有5-30％的患者持续疼痛或功能丧失。目前，没有 存在技术来增强术中癌症和神经识别。那就是提供的技术 直接实时直接可视化癌症和神经将大大改善手术 结果并减少HNSCC患者的合并症。荧光引导手术（FGS）已成功 整合到临床医学中，为外科医生提供重要时机和复杂的实时可视化 解剖学。使用紧凑型和高分辨率FGS成像系统，几乎完全在 近红外（NIR，700-900 nm），外科医生可以对靶向荧光探针进行高对比度的靶向荧光探针 厘米深度。正在开发的NIR神经特异性和HNSCC靶向的探针将共同提供 用于HNSCC切除的集成FGS工具。几个基于胡椒的FGS成像问题已经证明了 识别肿瘤边缘的功效，目前处于II和III期临床试验中，包括针对性的临床试验 表皮生长因子受体（EGFR），基质金属蛋白酶（MMP）和整联蛋白。我们已经发展了 一流的NIR神经特异性荧光小分子问题，这些问题表现出高神经信号 背景组织（例如肌肉，脂肪，脉管系统，筋膜等）在静脉内给药后 啮齿动物和猪。重要的是，针对肿瘤的FGS问题利用以800 nm为中心的荧光记者 波长，而我们的神经特异性探针在700 nm波长下荧光，提供了频谱不同的 组织检测和与现有两色FGS系统的兼容性。这两个的结合 有希望的技术将提供一种全面的创新解决方案，以增强癌症控制 和HNSCC切除过程中的紧张差异。这项研究的直接里程碑将包括（1） 对头部和颈部手术的铅NIR神经特异性荧光团的表征，（2） 肿瘤和神经特异性FGS探针共同给药表现，包括串扰，（3）评估 该技术使用临床两色FGS系统。这项工作将导致第一个全面的FGS工具 用于癌症切除和头颈手术过程中的神经保留。拟议的发展将 为进一步的发展和伙伴关系提供重要的概念验证。在第二阶段，第一个两色​​肿瘤 在接受HNSCC切除的患者中，将完成针对性的FGS研究。